scholarly journals The Evolution in The Treatment of Multiple Myeloma Towards Targeted Magnetic Molecularly Imprinted Nanomedicines

2015 ◽  
pp. 1-2
Author(s):  
Edgar Pérez-Herrero
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bacterial Infections ◽  
Plasma Cells ◽  
The Body ◽  
Western World ◽  
Bone Lesions ◽  
Non Hodgkin Lymphoma ◽  
Clonal Proliferation ◽  
Tract Infections

Multiple myeloma is the second more frequently haematological cancer in the western world, after non-Hodgkin lymphoma, being about the 1-2 % of all the cancers cases and the 10-13% of hematologic diseases. The disease is caused by an uncontrolled clonal proliferation of plasma cells in the bone marrow that accumulate in different parts of the body, usually in the bone marrow, around some bones, and rarely in other tissues, forming tumor deposits, called plasmocytomas. This uncontrolled clonal proliferation of plasma cells produces the secretion of an abnormal monoclonal immunoglobulin (paraprotein or M-protein) and prevents the formation of the other antibodies produced by the normal plasma cells that are destroyed. The anormal secretion of paraproteins unbalance the osteoblastosis and osteoclastosis processes, leading to bone lesions that cause lytic bone deposits and the release of calcium from bones (hypercalcemia) that may produce renal failure. Regions affected by bone lesions are the skull, spine, ribs, sternum, pelvis and bones that form part of the shoulders and hips. The substitution of the healthy bone marrow by infiltrating malignant cells and the inhibition of the normal production of red blood cells produce anaemia, thrombocytopenia and leukopenia. Multiple myeloma patients are immunosuppressed because of leukopenia and the abnormal immunoglobulin production caused by the uncontrolled clonal proliferation of plasma cells, being susceptible to bacterial infections, like pneumonias and urinary tract infections. The interaction of immunoglobulin with hemostatic mechanisms may lead to haemorrhagic diathesis or thrombosis. Also, disorders of the central and peripheral nervous system are part of the disease, being the more common neurological manifestations the spinal cord compressions and the peripheral neuropathies.

scholarly journals Mieloma multipel: aspek patogenesis molekuler

2019 ◽  
Vol 3 (1) ◽  
pp. 1-7
Author(s):  
Made Bakta
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Germinal Center ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Somatic Hypermutation ◽  
P53 Mutation ◽  
Bone Lesions ◽  
Genetic Changes ◽  
Clonal Proliferation

Multiple myeloma (MM) is a neoplastic plasma disorder that is characterized by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein in the blood or urine and associated organ dysfunction. It is preceded by a premalignant tumor which is share genetic abnormalities, monoclonal gammopathy of undetermined significance (MGUS). Although remarkable progress has been achieved, but pathogenesis of MM is still very complex. Multiple myeloma appears to arise from the malignant transformation of germinal-center B-lymphocyte. The first oncogenic events in MM appear to occur in the germinal center due to error in isotype class switching and somatic hypermutation. MM is divided into two distinct genetic subtypes: (1) hyperdiploid myeloma is characterized by multiple trisomies of chromosome 3, 5, 7, 9, 11, 15, 19 and 21; (2) non-hyperdiploid in contrast is characterized by recurrence translocations t(4;14), t(14;16), t (14;20); t(6;14) and t(11;14). A unifying event in the pathogenesis of MM is the dysregulated expression of cyclin D gene. Genetic aberrations occur in MM and also in premalignant state (MGUS), suggesting that genetic mutations alone are necessary, but not sufficient for myeloma transformation. A “ random second hit model” was proposed. Hypothetical second hits are: additional genetic changes ( RAS mutation, p16 methylation, p53 mutation), proliferation due to cell cycle dysregulation, evasion of programmed cell death and changes in bone marrow microenvironment. A complex interaction with the BM microenvironment , characterized by activation of osteoclast and supression of osteoblast , leads to lytic bone lesions. 

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

Multiple Myeloma Associated GI Polyposis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5009-5009
Author(s):  
Nassim Nabbout ◽  
Mohamad El Hawari ◽  
Thomas K. Schulz
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Bone Marrow Failure ◽  
Bone Lesions ◽  
Rare Manifestation ◽  
History Of ◽  
Central Ulceration

Abstract Abstract 5009 Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells that can result in osteolytic bone lesions, hypercalcemia, renal impairment, bone marrow failure, and the production of monoclonal gammopathy. The gastrointestinal tract is rarely involved in myeloma. GI polyposis is a rare manifestation of extra-medullary disease in multiple myeloma. Such cases usually present as gastrointestinal hemorrhage or intestinal obstruction. A 53-year-old African American male recently diagnosed with multiple myeloma presented with three-day history of rectal bleed and fatigue. EGD showed multiple raised, polypoid, rounded lesions with a superficial central ulceration in the stomach. Colonoscopy showed similar lesions in the ascending and transverse areas of the colon that ranged in size from 5 to 16 mm in diameter. Biopsies showed that these polyps were made of plasma cells. A bone marrow biopsy showed diffuse involvement (greater than 90%) of bone marrow with multiple myeloma with anaplastic features. The patient was started on bortezomib at diagnosis, however, he passed away a few weeks later. This type of metastatic disease has been described in isolated case reports in the literature, while solitary GI plasmacytoma has been reported more frequently. In rare cases, multiple myeloma can involve the GI tract which may lead to bleed or obstruction. This involvement is likely a marker of aggressivity. This example of extra-medullary disease in myeloma is an uncommon variant with features of poor prognosis and dedifferentiation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Case Report: Multiple Vertebral Compression Fractures in 14-Year-Old Children With Multiple Myeloma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xia Wang ◽  
He He ◽  
Mei Zhang ◽  
Chuan Li ◽  
Chengyao Jia
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Case Report ◽  
Plasma Cells ◽  
Vertebral Compression Fractures ◽  
Good Clinical Response ◽  
Hematopoietic Stem ◽  
Compression Fractures ◽  
Clonal Proliferation ◽  
Chinese Case

Multiple myeloma (MM) is a neoplastic disorder characterized by clonal proliferation of malignant plasma cells derived from B cells in bone marrow. Pediatric MM is rare with only approximately 0.3% of cases diagnosed before the age of 30. In this report, we present a 14 years old boy diagnosed as MM with multiple pathologic vertebral fractures. To our knowledge, our patient is the youngest Chinese case in the literature to present with MM. He was treated with bortezomib, dexamethasone, and cyclophosphamide followed by autologous hematopoietic stem cell transplantation with good clinical response. We hope to aid in the understanding of the pathophysiology and management of this condition.

scholarly journals Is There Any Relationship between Human Herpesvirus-8 and Multiple Myeloma?

Lymphoma ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Mohammad Hadi Sadeghian ◽  
Maryam Mohammadnia Avval ◽  
Hossein Ayatollahi ◽  
Mohammad Reza Keramati ◽  
Bahram Memar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Human Herpesvirus ◽  
The Body ◽  
Human Herpesvirus 8 ◽  
Bone Marrow Biopsies ◽  
Exact Test ◽  
Herpesvirus 8

Background. Human herpesvirus-8 (HHV-8) is associated with some human diseases including Kaposi’s sarcoma and also some B-cell lymphoproliferative disorders. Few studies have highlighted the potential role of HHV-8 in the development of multiple myeloma (MM) which is known as a malignant proliferation of plasma cells derived from a single clone. Aims. The aim of this study was to find a relationship between HHV-8 and MM using polymerase chain reaction (PCR) method. Materials and Methods. This study was conducted on 30 formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies of multiple myeloma and 30 normal FFPE bone marrow biopsies. After the sample preparation, Deoxyribonucleic acid (DNA) was extracted by nonheating procedure. PCR for HHV-8 virus was carried out with commercial kit and the PCR products were visualized by gel electrophoresis. Finally, the statistical analysis was performed. Results. HHV-8 virus was not detected by PCR from FFPE blocks of multiple myeloma samples, while only one of the controls showed DNA band of the corrected molecular weights. Fisher’s exact test showed that no statistical differences were found between the two groups (P=0.999). Conclusion. Our report adds to the body of evidence that there is no association between HHV- 8 and MM against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation.

scholarly journals Association of Multiple Myeloma and Giant Cell Arteritis – A Case Report

2020 ◽  
Author(s):  
Rui Marques Osório ◽  
Sérgio Pina ◽  
Teresa Salero ◽  
Margarida Viana Coelho ◽  
Domingos Sousa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Plasma Cells ◽  
Lymphoproliferative Disorders ◽  
Medicine Department ◽  
Clonal Proliferation ◽  
Bone Marrow Plasma

Autoimmune diseases (AID) have been associated with a variety of lymphoproliferative disorders. Multiple myeloma (MM), one of the most common haematologic malignancies characterized by clonal proliferation of bone marrow plasma cells, has been associated with a range of autoimmune disorders. In this report, we described a case study of a patient admitted to our Internal Medicine Department for a bone marrow biopsy and myelogram due to a monoclonal peak observed by his general practitioner. However, at admission he presented typical giant cell arteritis (GCA) complaints, suggesting the coexistence of both diseases. The possible pathogenesis, as found in the literature, explaining the association will be discussed.

scholarly journals Targeting the Resistance in Multiple Myeloma

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 3
Author(s):  
Freitas ◽  
Issa ◽  
Cuendet
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cancer Stem Cells ◽  
Plasma Cells ◽  
Therapeutic Strategies ◽  
High Rate ◽  
Hematological Cancer ◽  
Clonal Proliferation ◽  
Low Incidence

Multiple myeloma is a hematological cancer characterized by the clonal proliferation of malignant plasma cells in the bone marrow. That disease has a rather low incidence but displays a high rate of relapse and resistance to conventional therapies. It is therefore necessary to find new therapeutic strategies to overcome this resistance, which is partly attributed to a subpopulation of cells known as cancer stem cells. Withanolides and HDAC6 selective inhibitors were identified as promising compounds in various resistant multiple myeloma models.

scholarly journals Treatment Approaches of Multiple Myeloma

2021 ◽  
Author(s):  
Minyahil Alebachew Woldu ◽  
Atalay Mulu Fentie ◽  
Tamrat Assefa Tadesse
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Clinical Investigation ◽  
Malignant Neoplasm ◽  
Bone Destruction ◽  
Organ Damage ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
Newly Diagnosed

Multiple Myeloma (MM) is the most common malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Clinical investigation of MM requires the evaluation of bone marrow for plasma cell infiltration, and detection and quantification of monoclonal protein in the serum or urine, and evidence for end-organ damage (i.e., hypercalcemia, renal insufficiency, anemia, or bone lesions). The overall goal of treatment of MM is to improve survival. The treatment landscape and clinical outcome of MM have changed in the last two decades, with an improved median survival of 8–10 years. Management of MM involves induction, consolidation, and maintenance therapy. Currently, Autologous stem cell transplant (ASCT) is considered as the standard care of treatment for newly diagnosed fit MM patients. Multiple combinations of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) such as Thalidomide, lenalidomide, and pomalidomide have been under evaluation in ASCT-eligible and ineligible settings, and studies are still ongoing. For patients with ASCT-eligible newly diagnosed MM, induction therapy with triple drugs should contain an IMiD, a PI, and a corticosteroid, usually lenalidomide-bortezomib-dexamethasone. For ASCT-ineligible patients on lenalidomide with dexamethasone (Rd), with addition of bortezomib or daratumumab can be considered.

Modulation of Proinflammatory Cytokines and Insulinlike Growth Factor-1 (IGF-1) in Human Immunodeficiency Virus-1 Smoldering Multiple Myeloma (HIVSMM) Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5043-5043
Author(s):  
Eugene McPherson ◽  
Philippe Tassy
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Viral Load ◽  
Growth Factor ◽  
Cell Count ◽  
Proinflammatory Cytokines ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Cd4 Cell Count ◽  
Cd4 Cell

Abstract Abstract 5043 Multiple myeloma is a B-cell malignancy involving germinal center B cells characterized by blood and urinary monoclonal proteins, osteolytic bone lesions and infiltration of bone marrow with plasma cells wit pathology involving aberrant chromosomal translocation with increased glucose uptake (Warburg Phenomena). This glucose transporter (GLUT) is activated and over expressed along with proinflammatory cytokines produced by malignant plasma cells both smoldering and multiple myeloma (MM). These cytokines may control growth, progression and dissemination. Interleukin-6 (IL-6) is a major cytokinetic growth factor in MM but IGF-1 is a more prominent growth factor that binds to IGF-1 receptor (IGF-1R) and is a strong indicator of prognosis which can augment anti-apoptotic effects of IL-6. Modulation of IGF-1 and proinflammatory cytokines in HIVSMM patients with ritonavir-based highly active antiretroviral therapy (RTV-based HAART) may suppress nuclear factor kappa b (NF Kb) and inhibit the overexpression of GLUT-1–4 required for HIVSMM growth and viability. A selenium adjuvant RTV-based HAART abrogates GLUT activity with specificity for GLUT-4 (prominent growth factor in MM cells. We present a 44 YOF with an with HIV disease, anemia, CD4 cell count of 74/cumm, viral load > 1 million copies/ml, SMM with IgG kappa/lambda 3. 68 grams/L, a hypocellular bone marrow biopsy with > 60 % plasma cell (polytypic) and with an increase in immature forms. Her serum free light chains (SFLC) on diagnosis was 324 mg/dl/121 mg/dl kappa/lambda ratio of 2. 68, bone scan with no evidence of lytic lesions and beta-2-microglobulin (B2MG) of 14. 40 mg/L: soluble interleukin-2 receptor (sIL2R) of 10, 833. 47 pg/ml; IGF-1 was 346 ng/ml (Nl = 94–250 ng/ml); selenium level was 137 mg/dl; C-reactive protein (CRP) of 38 mg/dl. After three years of selenium-RTV-based-HAART therapy her proinflammatory markers trended downward. CD4 cell count now is 348/cumm; viral load of 25. 7 copies/ml; SMM IgG 0. 972 grams/L; SFLC of 35. 9mg/dl/35mg/dl kappa/lambda ratio of 1. 03; B2MG of 2. 24 mg/L; sIL2R of 6546. 14 pg/ml; IGF-1 of 128 ng/ml; selenium of 150mg/dl; and CRP of 0. 26 mg/dl. Conclusions: Modulation of myeloma proinflammatory cytokines with protease inhibitor RTV, selenium adjuvant based HAART in HIVSMM patients may suppress the GLUT OVEREXPRESSION activity and prevent development TUMORGENESIS OF MM. Disclosures: No relevant conflicts of interest to declare.

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